L2 - Lecture 2: Axon guidance (outline) I. The axon growth...

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Lecture 2: Axon guidance (outline) I. The axon growth cone: structure and motility II. Axon guidance signals: A. Non-diffusible signals: cell adhesion molecules, extracellular matrix molecules B. Diffusible signals: chemo-attraction or repulsion III. Classic experiments: A. netrin and DCC: attract commissural axons B. Slits and Robo: repel commissural axons after they crossed the midline (for paper discussion) Required reading: Purves et al. Ch23 (p577-590), Supplemental readings: Bear et al. Ch23 (p697-702) Netrin/DCC review: Moore et al (2007) Adv Exp Med Biol 621:17 Chemoaffinity hypothesis: Meyer RL (1998) Neuropsycholgia 36:957
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A cultured sensory neuron extending a growth cone with long thin filopodia http://www.bio.miami.edu/ktosney/images/ResHomSEMgc.jpg I. Growth cones - The growing tip of a neurite is called the growth cone . They appear as an enlargement of the shaft of the axon.
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I. Growth cones - The growing tip of a neurite is called the growth cone . They appear as an enlargement of the shaft of the axon. - Originally documented by Ramon y Cajal based upon stationary images; In 1910, Ross G. Harrison first observed axons extending in a living tadpole.
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I. Growth cones - The growing tip of a neurite is called the growth cone . They appear as an enlargement of the shaft of the axon. - Originally documented by Ramon y Cajal based upon stationary images; In 1910, Ross G. Harrison first observed axons extending in a living tadpole. Cajal: growth cones from sensory relay neurons in dorsal spinal cord. Notes: different shapes of the growth cones, simpler when it is close to origin (C ->A).
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I. Growth cones (cont.) - Filopodia and lamellipodia are filled with actin. Actin cytoskeleton : regulate lamellipodial and filopodial shape and growth. Microtubules cytoskeleton : regulate axon elongation. Filamentous actin (F-actin): seem in lamelipodia and filopodia. Tyrosinated microtubules: primary tubular constituents of the lamellar region. Acetylated microtubules: restricted to axons.
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I. Growth cones (cont.) - Filopodia and lamellipodia are filled with actin and highly motile. Mauther neurons in the hindbrain of a zebrafish embryo. Insert: Cross at midline and go down along spinal cord. Right: extension speed ~50 m m in ~35min.
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I. Growth cones (Cont.) - Filopodia and lamellipodia are filled with actin and highly motile. - The leading process of the growth cone is flattened and has few organelles; While the body of the growth cone is packed with microtubules, mitochondria and other organelles. Aplysia bag cell growth cone Stephen Smith, Stanford U
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Structure of growth cone - Actin and microtubules. Balance between monomeric globular-actin (G-actin) and tubulin vs. polymerized actin filaments (F-actin) and microtubules is regulated by their binding proteins in response to extracellular cues.
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Assembly and disassembly of actin or tubulin is influenced by intracellular Ca. Ca concentration can be regulated via voltage-sensitive Ca channels or transient
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L2 - Lecture 2: Axon guidance (outline) I. The axon growth...

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